Abstract
Striatal dopamine is thought to play a fundamental role in the reinforcing effects of tobacco smoking and nicotine. Microdialysis studies indicate that nicotine also increases dopamine in extrastriatal brain areas but much less is known about its role in addiction. High affinity D2/3 receptor radiotracers permit the measurement of cortical dopamine in humans using Positron Emission Tomography (PET). [(11)C]FLB-457 PET scans were conducted in ten nicotine-dependent daily smokers after overnight abstinence and reinstatement of smoking. Voxel-wise [(11)C]-FLB-457 binding potential (BPND) in the frontal lobe, insula and limbic regions was estimated in the two conditions. Paired t-tests showed BPND values were reduced following smoking (an indirect index of dopamine release). The overall peak t was located in the cingulate gyrus which was part of a larger medial cluster (BPND change -12.1±9.4%) and this survived FDR correction for multiple comparisons. Clusters were also identified in the left anterior cingulate cortex / medial frontal gyrus, bilateral prefrontal cortex (PFC), bilateral amygdala and left insula. This is the first demonstration of tobacco smoking-induced cortical dopamine release in humans; it may be the result of both pharmacological (nicotine) and non-pharmacological factors (tobacco cues). Abstinence increased craving but had minimal cognitive effects thus limiting correlation analyses. However, given that the cingulate cortex, PFC, insula and amygdala are thought to play important roles in tobacco craving, cognition and relapse, these associations warrant investigation in a larger sample. [(11)C]FLB-457 PET imaging may represent a useful tool to investigate individual differences in tobacco addiction severity and treatment response.Neuropsychopharmacology accepted article preview online, 15 December 2014. doi:10.1038/npp.2014.327.